Fig. Changes in the plasma concentration of r-hirudin, as determined by the ecarin clotting time, during intermittent haemodiafiltration (HDF), using a high-flux dialyser Ordering has never been so easy: http://www.schattauer.com

The general pathophysiological basis in occlusive arterial disease is the reduced flow rate of blood in the microcirculation. Blood flow in the ischemic tissue can be increased by improving the flow properties of blood. The fibrinogen concentration of blood and the deformability of red cells are two main factors determining the flow properties of blood. Ancrod, a fibrinogen-lowering substance, improves the flow properties of blood by decreasing the viscosity of blood and plasma and by desaggregation of erythrocyte aggregates. Treatment of patients suffering from severe occlusive arterial diseases with Ancrod exhibits surprisingly good results. Disappearance of rest pains and reduction in the use of analgetic drugs has been proved statistically. In the exercising muscles a local hyperosmolarity exists, which is able to decrease the deformability of red cells thereby impairing the flow in narrow capillaries. The addition of Pentoxifyllin to blood in-vitro reduces the rigidity of red cells in hyperosmolar blood samples by increasing their cellular ATP-content. Thus the reduced flow rate of hyperosmolar blood through 8 mu-capillaries could be increased twice (p less than 0.0005) by the addition of Pentoxifyllin. These in-vitro results could be the starting point of a new idea for the treatment of patients with intermittent claudication.

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Local tissue oxygen pressure was measured with micro-Pt-electrodes in the resting tibialis anterior muscles of 10 patients with chronic occlusive arterial disease and in 9 healthy subjects. The mean pO2 values in the patient group was 13.3 +/- 5.4 Torr, and 27.2 +/- 4.4 Torr in the control group. The difference is highly statistically significant. Preliminary results of treatment of 10 patients with the rheologically-active drug Ancrod show a statistically significant increase of oxygen pressure in the ischemic muscle tissue. Measurement of muscle tissue pO2 with microelectrodes seems to be an objective and quantitative method to investigate the oxygen supply to ischemic muscles and to judge the effects of therapeutic measures.

Recent investigations have revealed that erythrocytes from patients with chronic arterial occlusive disease are significantly less deformable than red blood cells from healthy subjects. The influence of pentoxifylline on red blood cell fluidity was measured by a standard filtration technique using 8 micron membrane filters. Impaired deformability of erythrocytes was significantly improved in patients suffering from peripheral vascular disorders following intravenous injection of 200 mg pentoxifylline. Studies on reduced red cell deformability induced by hyperosmolarity in vitro showed that pentoxifylline (4 and 20 microgram/ml) produced a dose-dependent improvement both in blood from healthy subjects and from patients with peripheral arterial occlusive disease. The results suggest that the positive therapeutic effect of pentoxifylline in peripheral arterial occlusive disease is mediated by improving red cell fluidity in the microcirculation.